João Pedro Ferreira1,2, Nicolas Girerd3, Pedro Bettencourt Medeiros4, Mário Santos5,4, Henrique Cyrne Carvalho4, Paulo Bettencourt6, David Kénizou7, Javed Butler8, Faiez Zannad3, Patrick Rossignol3. 1. INSERM, Centre D'Investigations Cliniques 1433, INSERMU116, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, 4 Rue du Morvan, Vandoeuvre lès Nancy, 54500, Nancy, France. jp7ferreira@hotmail.com. 2. Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal. jp7ferreira@hotmail.com. 3. INSERM, Centre D'Investigations Cliniques 1433, INSERMU116, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, 4 Rue du Morvan, Vandoeuvre lès Nancy, 54500, Nancy, France. 4. Centro Hospitalar do Porto, Porto, Portugal. 5. Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal. 6. Centro Hospitalar São João, Porto, Portugal. 7. Service de cardiologie, hôpital E.-Muller, 20, rue du Docteur-Laennec, BP 1070, 68070, Mulhouse Cedex, France. 8. Division of Cardiology, Department of Medicine, Stony Brook University, Stony Brook, NY, USA.
Abstract
INTRODUCTION: Loop diuretic resistance characterized by inefficient sodium excretion complicates many patients with acutely decompensated heart failure (ADHF). Mineralocorticoid receptor antagonists (MRAs) in natriuretic doses may improve spot urine sodium excretion and outcomes. OBJECTIVE: Our primary aim was to assess the association of high-dose spironolactone with short-term spot urine sodium excretion, and our secondary aim was to determine if this higher short-term spot urine sodium excretion is associated with reduction in the composite clinical outcome (of cardiovascular mortality and/or ADHF hospitalization) event rate at 180 days. METHODS: Single-centre, non-randomized, open-label study enrolling 100 patients with ADHF. Patients were treated with standard ADHF therapy alone (n = 50) or oral spironolactone 100 mg/day plus standard ADHF therapy (n = 50). Spot urine samples were collected at day 1 and day 3 of hospitalization. RESULTS: Spironolactone group had significantly higher spot urine sodium levels compared to standard care group at day 3 (84.13 ± 28.71 mmol/L vs 70.74 ± 34.43 mmol/L, p = 0.04). The proportion of patients with spot urinary sodium <60 mmol/L was lower in spironolactone group at day 3 (18.8 vs 45.7, p = 0.01). In multivariate analysis, spironolactone was independently associated with increased spot urinary sodium and urinary sodium/potassium ratio of >2 at day 3 (both, p < 0.05). Higher spot urine sodium levels were associated with a lower event rate [HR for urinary sodium >100 mmol/L = 0.16 (0.06-0.42), p < 0.01, compared to <60], and provided a significant prognostic gain measured by net reclassification indexes. CONCLUSION: Spot urinary sodium levels >60 mmol/L and urinary sodium/potassium ratio >2 measured at day 3 of hospitalization for ADHF are associated with improved mid-term outcomes. Spironolactone is associated with increased spot urinary sodium and sodium/potassium ratio >2.
INTRODUCTION: Loop diuretic resistance characterized by inefficient sodium excretion complicates many patients with acutely decompensated heart failure (ADHF). Mineralocorticoid receptor antagonists (MRAs) in natriuretic doses may improve spot urine sodium excretion and outcomes. OBJECTIVE: Our primary aim was to assess the association of high-dose spironolactone with short-term spot urine sodium excretion, and our secondary aim was to determine if this higher short-term spot urine sodium excretion is associated with reduction in the composite clinical outcome (of cardiovascular mortality and/or ADHF hospitalization) event rate at 180 days. METHODS: Single-centre, non-randomized, open-label study enrolling 100 patients with ADHF. Patients were treated with standard ADHF therapy alone (n = 50) or oral spironolactone 100 mg/day plus standard ADHF therapy (n = 50). Spot urine samples were collected at day 1 and day 3 of hospitalization. RESULTS:Spironolactone group had significantly higher spot urine sodium levels compared to standard care group at day 3 (84.13 ± 28.71 mmol/L vs 70.74 ± 34.43 mmol/L, p = 0.04). The proportion of patients with spot urinary sodium <60 mmol/L was lower in spironolactone group at day 3 (18.8 vs 45.7, p = 0.01). In multivariate analysis, spironolactone was independently associated with increased spot urinary sodium and urinary sodium/potassium ratio of >2 at day 3 (both, p < 0.05). Higher spot urine sodium levels were associated with a lower event rate [HR for urinary sodium >100 mmol/L = 0.16 (0.06-0.42), p < 0.01, compared to <60], and provided a significant prognostic gain measured by net reclassification indexes. CONCLUSION: Spot urinary sodium levels >60 mmol/L and urinary sodium/potassium ratio >2 measured at day 3 of hospitalization for ADHF are associated with improved mid-term outcomes. Spironolactone is associated with increased spot urinary sodium and sodium/potassium ratio >2.
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